Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma.
EGCG is a flavonoid that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, A172 and U251) were treated with EGCG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of EGCG in combination with TRAIL induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. EGCG treatment down-regulated phosphoprotein-enriched in astrocytes (PEA15) through an Akt (PKB)-dependent mechanism. In addition, over-expression of PEA15 attenuated cytotoxicity induced by the combination of EGCG and TRAIL. In summary, PEA15 is a key regulator in TRAIL-EGCG-mediated cell death in malignant glioma.
Siegelin
M D
MD
Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany. markus.siegelin@med.uni-heidelberg.de
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D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D053179:Caspase 7 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; D002392:Catechin; C045651:epigallocatechin gallate; D053179:Caspase 7